The N-linked oligosaccharide moieties of glycoproteins function in vivo to protect the protein from proteolysis, to increase its solubility, and to target it to specific cells. The high specificity of the cell targeting function is achieved by binding of the saccharide portion to endogenous lectins, which are usually narrowly distributed in a single organ or cell type. While several hundred different N-linked oligosaccharide structures have been identified on serum, cell surface, and intracellular proteins, comparatively few mammalian lectins have been well characterized. The ligand for asialoglycoprotein receptor of rat hepatocytes is a single triantennary oligosaccharide which binds stereospecifically and with high-affinity to this lectin. These results support the hypotheses that: (a) each N-linked oligosaccharide potentially functions uniquely in binding optimally to a tissue-specific lectin, (b) subtle differences in carbohydrate structure influence the relative affinity of oligosaccharides for mammalian lectins and dramatically alter serum half-life and targeting site, and (c) more lectins which function as specific receptors for N-linked oligosaccharides await discovery. To reveal the location and binding specificity of these putative lectins and define the tissue targeting specificity that N-linked oligosaccharides exert on glycoproteins, a series of well defined N-linked oligosaccharides will be prepared. The blood clearance profile of radiolabeled oligosaccharides administered intravenously to mice and rats will be analyzed. The organ biodistribution will be measured using whole animal autoradiography and tissue combustion analysis. Reversible linking agents will be utilized to optimize lysosomal release of drugs. Glycopeptides are attractive as drug-carriers because they are: the minimal natural structure that binds with high affinity and specificity to an endogenous lectin, low molecular weight, highly purified, non-antigenic, biodegradable, and utilize natural endocytosing receptors for oligosaccharide internalization and drug release in the target cell.